This project utilizes the erythropoietin-induced switch in hemoglobin phenotype which occurs in sheep and goats as a model system for understanding factors which regulate globin gene expression in erythroid cells. Both the cellular events accompanying differentiation and hemoglobin synthesis and the subcellular events related to the regulation of transcription will be explored. The marrow fractionation studies will be extended to determine if a population of precursor cells can be obtained which is capable of generating colonies producing only hemoglobin C. The relationship between the duration of exposure to high concentration erythropoietin and the production of hemoglobin C will be defined to determine if commitment to hemoglobin phenotype is an irreversible event. Synthesis of specific hemoglobins in human colonies will be examined.